The experiments described in this proposal provide a comprehensive examination of electrolyte transfer characteristics in erythrocyte membranes obtained from patients with affective disorders. Our previous studies with the lithium ion (Li ion) have led us to hypothesize that some depressed patients have a genetically-determined defect in cell membrane properties regulating monovalent transfer. Thus, Li ion accumulated to a greater extent in erythrocytes of bipolar as opposed to unipolar patients and in patients who responded to the "prophylactic" effect of Li ion as compared to nonresponders. A prospective study intended to extend and confirm this latter observation is outlined. It may be that differences in Li ion accumulation by erythrocytes illuminates an intrinsic alteration in cell membrane functioning. This possibility will be explored by measuring the kinetics of Li ion transfer across the erythrocyte membrane, as well as that of labelled sodium and rubidium ions. Furthermore, we shall study the effect of low concentrations of Li ion on electrolyte transport systems of human red cells and animal nerves.